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Guide
Drug Safety-related Labeling Changes (SrLC) Database
| ANDA | Abbreviated New Drug Application |
| BLA | Biologics License Application |
| CDER | Center for Drug Evaluation and Research |
| MG | Medication Guide |
| NDA | New Drug Application |
| PCI | Patient Counseling Information |
| PI | Patient Information |
| PLR | Physician Labeling Rule |
| PLLR | Pregnancy and Lactation Labeling Rule |
| Italics | For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
| Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
| BW | Box Warning |
| WP | Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
| AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
| DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
| USP | Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
| PCI/PI/MG | Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
PERIKABIVEN IN PLASTIC CONTAINER (NDA-200656)
(AMINO ACIDS; CALCIUM CHLORIDE; DEXTROSE; MAGNESIUM SULFATE; POTASSIUM CHLORIDE; SODIUM ACETATE; SODIUM GLYCEROPHOSPHATE; SOYBEAN OIL)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
07/24/2025 (SUPPL-24)
5 Warnings and Precautions
5.4 Hypersensitivity Reactions
Additions and/or revisions underlined:
. . .
In postmarketing experience, anaphylaxis has been reported following PERIKABIVEN administration [see Adverse Reactions (6.2)].
. . .
6 Adverse Reactions
6.2 Postmarketing Experience
Additions and/or revisions underlined:
. . .
Immune system disorders: hypersensitivity reactions, including anaphylaxis [see Contraindications (4), Warnings and Precautions (5.4)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or revisions underlined:
. . .
Hypersensitivity Reactions
Inform patients and caregivers that PERIKABIVEN may cause hypersensitivity reactions, including anaphylaxis. If PERIKABIVEN is infused at home, instruct patients or caregivers to stop the infusion of PERIKABIVEN immediately and seek medical attention if they experience signs or symptoms of a hypersensitivity reaction, such as rapid or weak heartbeat, feeling faint, difficulty in breathing or swallowing, vomiting, nausea, headache, sweating, dizziness, hives, rash, itching, flushing, dizziness, fever, or chills [see Warnings and Precautions (5.4)].
. . .
05/17/2023 (SUPPL-18)
4 Contraindications
(Additions and/or revisions underlined)
The use of PERIKABIVEN is contraindicated in:
· Neonates (28 days of age or younger) receiving concomitant treatment with ceftriaxone, even if separate infusion lines are used, due to the risk of fatal ceftriaxone calcium salt precipitation in the neonate’s bloodstream [see Limitations of Use (1), Warnings and Precautions (5.5), Use in Specific Populations (8.4)].
· Patients with known hypersensitivity to egg, soybean, peanut or any of the active or inactive ingredients in PERIKABIVEN [see Warnings and Precautions (5.4)];
· Patients with severe disorders of lipid metabolism characterized by hypertriglyceridemia (serum triglyceride concentration >1,000 mg/dL) [see Warnings and Precautions (5.10)].
5 Warnings and Precautions
5.1 Clinical Decompensation with Rapid Infusion of Intravenous Lipid Emulsion in Neonates and Infants
(Additions and/or revisions underlined)
In the postmarketing setting, serious adverse reactions including acute respiratory distress, metabolic acidosis, and death have been reported in neonates and infants after rapid infusion of intravenous lipid emulsions. Hypertriglyceridemia was commonly reported.
5.14 Monitoring/Laboratory Tests
(Additions and/or revisions underlined)
Monitor fluid status closely in patients with pulmonary edema or heart failure.
Throughout treatment, monitor serum triglycerides [see Warnings and Precautions (5.13)], fluid and electrolyte status, serum osmolarity, blood glucose, liver and kidney function, blood count (including platelets), and coagulation parameters.
PERIKABIVEN contains Vitamin K that may counteract anticoagulant activity [see Drug Interactions (7)].
The lipids contained in PERIKABIVEN may interfere with some laboratory tests (e.g., hemoglobin, triglycerides, lactate dehydrogenase, bilirubin, and oxygen saturation) if blood is sampled before the lipids in PERIKABIVEN have cleared from the bloodstream. Conduct these tests at least 6 hours after stopping the infusion.
6 Adverse Reactions
(Additions and/or revisions underlined)
The following serious adverse reactions are discussed in greater detail in other sections of the prescribing information.
· Clinical Decompensation with Rapid Infusion of Intravenous Lipid Emulsion in Neonates and Infants [see Warnings and Precautions (5.1)].
· Parenteral Nutrition-Associated Liver Disease and Other Hepatobiliary Disorders [see Warnings and Precautions (5.2)].
· Pulmonary Embolism and Respiratory Distress due to Pulmonary Vascular Precipitates [see Warnings and Precautions (5.3)].
· Hypersensitivity Reactions [see Warnings and Precautions (5.4)].
· Precipitation with Ceftriaxone [see Warnings and Precautions (5.5)].
· Infections [see Warnings and Precautions (5.6)].
· Fat Overload Syndrome [see Warnings and Precautions (5.7)].
· Refeeding Syndrome [see Warnings and Precautions (5.8)].
· Diabetes and Hyperglycemia [see Warnings and Precautions (5.9)].
· Hypertriglyceridemia [see Warnings and Precautions (5.10)].
· Vein Damage and Thrombosis [see Warnings and Precautions (5.11)].
· Electrolyte Imbalance and Fluid Overload in Patients with Decreased Renal Function [see Warnings and Precautions (5.12)].
· Aluminum Toxicity [see Warnings and Precautions (5.13)].
8 Use in Specific Populations
8.4 Pediatric Use
(Additions and/or revisions underlined)
The safety and effectiveness of PERIKABIVEN has not been established in pediatric patients of any age. In the postmarketing setting, clinical decompensation with rapid infusion of intravenous lipid emulsion in neonates and infants, sometimes fatal has been reported [see Warnings and Precautions (5.1)]. Patients, particularly preterm infants, are at risk for aluminum toxicity [see Warnings and Precautions (5.13)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(Additions and/or revisions underlined)
Inform patients and caregivers that pulmonary vascular precipitates causing pulmonary emboli (including some fatalities) and presenting as respiratory distress have been reported in patients receiving parenteral nutrition. If PERIKABIVEN is infused at home, instruct patients or caregivers to visually inspect the prepared solution, the infusion set, and catheter for precipitates, prior to administration as well as periodically during the administration [see Warnings and Precautions (5.3)]
Hypersensitivity Reactions
Inform patients and caregivers that PERIKABIVEN may cause hypersensitivity reactions. If PERIKABIVEN is infused at home, instruct patients or caregivers to stop the infusion of PERIKABIVEN immediately and seek medical attention if a hypersensitivity reaction occurs [see Warnings and Precautions (5.4)].
Infections
Inform patients and caregivers that patients who receive PERIKABIVEN are at risk of infection. If PERIKABIVEN is infused at home, instruct patients or caregivers to ensure aseptic techniques are used for the preparation and administration of PERIKABIVEN and to monitor for signs and symptoms of infection [see Warnings and Precautions (5.6)].
Fat Overload Syndrome
Inform patients and caregivers that fat overload syndrome has been reported with the use of intravenous lipid emulsions. If PERIKABIVEN is infused at home, instruct patients or caregivers to stop PERIKABIVEN if signs or symptoms of fat overload syndrome occur [see Warnings and Precautions (5.7)].
Refeeding Syndrome
If the patient is severely malnourished, inform patients and caregivers that administering parenteral nutrition including PERIKABIVEN may result in refeeding syndrome [see Warnings and Precautions (5.8)].
Diabetes and Hyperglycemia
Inform patients and their caregivers that administration of dextrose at a rate exceeding the patient’s utilization rate may lead to hyperglycemia, hyperosmolar coma, and death [see Warnings and Precautions (5.9)].
Hypertriglyceridemia
Inform patients and their caregivers about the risks of hypertriglyceridemia with PERIKABIVEN use [see Warnings and Precautions (5.10)].
06/28/2022 (SUPPL-14)
4 Contraindications
Additions and/or
revisions underlined:
The use of PERIKABIVEN is contraindicated in:
- Neonates (28 days of age or younger) receiving concomitant treatment with ceftriaxone, even if separate infusion lines are used, due to the risk of fatal ceftriaxone calcium salt precipitation in the neonate’s bloodstream [see Limitations of Use (1), Warnings and Precautions (5.5), Use in Specific Populations (8.4)].
- Patients with known hypersensitivity to egg, soybean proteins, peanut proteins, or to any of the active ingredients or excipients;
- Patients with severe hyperlipidemia or severe disorders of lipid metabolism characterized by hypertriglyceridemia (serum triglyceride concentration >1,000 mg/dL) [see Warnings and Precautions (5.13)].
- Patients with inborn errors of amino acid metabolism
- Patients with cardiopulmonary instability (including pulmonary edema, cardiac insufficiency, myocardial infarction, acidosis and hemodynamic instability requiring significant vasopressor support
- Patients with hemophagocytic syndrome
5 Warnings and Precautions
5.1 Death in Preterm Infants
Additions and/or revisions underlined:
Deaths in preterm
infants after infusion
of intravenous lipid emulsions containing only soybean oil have been reported in the
medical literature. Autopsy findings included intravascular lipid
accumulation in the lungs. Preterm and small-for-gestational-age infants have
poor clearance of intravenous lipid emulsion
and increased free fatty acid plasma levels following lipid emulsion infusion.
The safe and effective use of PERIKABIVEN injection in pediatric patients, including
preterm infants, has not been established. PERIKABIVEN is not recommended for use in pediatric patients
under the age of 2 years including preterm infants.
5.2 Parenteral Nutrition-Associated Liver Disease and Other Hepatobiliary Disorders
Newly added subsection:
Risk of Parenteral Nutrition-Associated Liver Disease
Parenteral nutrition-associated liver
disease (PNALD), also referred to as intestinal failure-associated liver disease (IFALD), can present as
cholestasis or hepatic steatosis, and may progress to steatohepatitis with
fibrosis and cirrhosis (possibly leading to chronic hepatic failure). The
etiology of PNALD is multifactorial; however, intravenously administered
phytosterols (plant sterols) contained in plant-derived lipid emulsions, such
as Intralipid (included in PERIKABIVEN), have been associated with development
of PNALD.
In a randomized study of neonates and infants expected to be treated with PN
for at least 28 days, parenteral nutrition-associated cholestasis (PNAC), a
precursor to PNALD, developed more frequently
in Intralipid-treated patients
than in patients
treated with a 4-oil mixed lipid emulsion
[see Adverse Reactions (6.1), Use
in Specific Populations (8.4)].Monitor liver tests in patients
treated with PERIKABIVEN and consider discontinuation or dosage
reduction if abnormalities occur.
Other Hepatobiliary Disorders
Hepatobiliary disorders including cholecystitis and cholelithiasis have developed in some PN-treated patients without preexisting
liver disease.
Monitor liver tests when administering PERIKABIVEN. Patients developing signs of hepatobiliary disorders should be assessed early to determine whether these conditions are related to PERIKABIVEN use.
5.3 Pulmonary Embolism and Respiratory Distress due to Pulmonary Vascular Precipitates
Newly added subsection:
Pulmonary vascular precipitates causing pulmonary emboli (including some fatalities) and respiratory distress have been reported in patients receiving parenteral nutrition.
Excessive addition of calcium and phosphate increases the
risk of the formation of calcium phosphate precipitates; however,
precipitates have been reported even in the absence of phosphate
salt in the solution. Precipitation following passage through an in-line filter
and suspected in vivo precipitate formation has also been reported.
Visually inspect the prepared solution, the infusion set, and catheter for
precipitates, prior to administration as well as periodically during the administration. If signs of respiratory distress
or pulmonary embolism occur, stop the PERIKABIVEN infusion and initiate
a medical evaluation.
5.4 Hypersensitivity Reactions
Additions and/or
revisions underlined:
PERIKABIVEN contains soybean
oil, which may cause hypersensitivity reactions. Cross reactions
have been observed between soybean and peanut. PERIKABIVEN is
contraindicated in patients with known hypersensitivity to egg, soybean, peanut
protein, or to any of the active or inactive ingredients in PERIKABIVEN . If a hypersensitivity reaction occurs,
stop infusion of PERIKABIVEN immediately and initiate appropriate treatment and
supportive measures.
5.5 Precipitation with Ceftriaxone
Additions and/or
revisions underlined:
Precipitation
of ceftriaxone-calcium can occur when ceftriaxone is mixed with
calcium-containing parenteral nutrition solutions, such as PERIKABIVEN in the same intravenous administration line. Do not
administer ceftriaxone simultaneously with PERIKABIVEN via a Y-site. However,
in patients other than neonates, ceftriaxone and PERIKABIVEN may be
administered sequentially if the infusion lines are thoroughly flushed between
infusions with a compatible fluid [see Dosage and Administration (2.1)].
Deaths have occurred in neonates (28 days of age or younger) who received concomitant intravenous calcium-containing solutions with ceftriaxone resulting from calcium-ceftriaxone precipitates in the lungs and kidneys, even when separate infusion lines were used [see Contraindications (4), Pediatric Use (8.4)].
5.6 Infections
Additions and/or
revisions underlined:
Parenteral nutrition, such as PERIKABIVEN, can support microbial growth and is an independent risk
factor for the development of catheter-related bloodstream
infections. To decrease the risk of infectious complications,
ensure aseptic techniques are used for catheter placement,
catheter maintenance, and preparation and administration of PERIKABIVEN.
Monitor for signs and symptoms of infection including fever and chills, as well as laboratory test results that might indicate infection (including leukocytosis and hyperglycemia). Perform frequent checks of the intravenous catheter insertion site for edema, redness, and discharge.
5.7 Fat Overload Syndrome
Additions and/or revisions
underlined:
Fat overload syndrome is a rare condition that has
been reported with intravenous lipid formulations.
and is characterized by a sudden deterioration in the patient's
condition (e.g., fever, anemia, leukopenia, thrombocytopenia,
coagulation disorders, hyperlipidemia, hepatomegaly, deteriorating liver function,
and central nervous
system manifestations such as coma). A reduced
or limited ability to metabolize lipids, accompanied
by prolonged plasma clearance (resulting in higher lipid levels), may result in
this syndrome. Although fat overload
syndrome has been most frequently observed when the recommended lipid dose or
infusion rate was exceeded, cases have also been described when the lipid
formulation was administered according to instructions.
If signs or symptoms of fat overload syndrome occur, stop PERIKABIVEN. The syndrome is usually reversible when the infusion of the lipid emulsion is stopped.
5.8 Refeeding Syndrome
Additions and/or
revisions underlined:
Administering PN to severely malnourished patients may result
in refeeding syndrome, characterized by the intracellular shift of potassium,
phosphorus, and magnesium as patients become anabolic.
Thiamine deficiency and fluid retention may also develop. To prevent these complications, closely monitor severely undernourished patients and slowly increase their nutrient intake.
5.9 Diabetes and Hyperglycemia
Additions
and/or revisions underlined:
Administration of dextrose at a rate
exceeding the patient’s utilization rate may lead to hyperglycemia, hyperosmolar
coma, and death. Monitor blood
glucose levels and treat hyperglycemia to maintain optimal glucose levels
while infusing PERIKABIVEN. Insulin may be administered or adjusted to maintain optimal
blood glucose levels
during PERIKABIVEN administration.
5.10 Laboratory Tests
Subsection title revised
Additions
and/or revisions underlined:
Monitor serum triglycerides [see Warnings
and Precautions (5.13)], essential fatty acids, fluid and
electrolyte status, serum osmolarity, blood glucose, liver tests, kidney
function, coagulation parameters, and complete blood count periodically
during treatment.
Supplementation of essential fatty acids may be needed.
5.11 Vein Damage and Thrombosis
Additions and/or revisions underlined:
The infusion of hypertonic nutrient injections into a peripheral vein may result in vein irritation, vein damage, and/or thrombosis. PERIKABIVEN is indicated for peripheral administration, or may be infused into a central vein; however, peripheral catheters should not be used for solutions with osmolarity of greater than or equal to 900 mOsm/L. The catheter should be removed as soon as possible if thrombophlebitis develops.
5.12 Electrolyte Imbalance and Fluid Overload in Patients with Decreased Renal Function
Subsection title revised
Additions
and/or revisions underlined:
Patients with decreased renal function, including those with pre-renal
azotemia, renal obstruction, or intrinsic renal disease, may be at increased risk of electrolyte
and fluid volume imbalance when receiving PN, including PERIKABIVEN. In
patients with decreased renal function with electrolyte imbalance or fluid overload,
the PERIKABIVEN dosage (e.g.,
fluid, protein, and electrolyte content) may require adjustment.
Monitor renal function
parameters. Patients developing signs of decreased renal function should
be assessed early by a clinician knowledgeable in renal disease in order
to determine the appropriate PERIKABIVEN dosage.
5.13 Hypertriglyceridemia
Additions and/or revisions underlined:
The use of PERIKABIVEN is contraindicated in patients with hypertriglyceridemia with serum triglyceride concentrations >1,000 mg/dL. Patients with conditions such as inherited lipid disorders, obesity, diabetes mellitus, or metabolic syndromes have a higher risk of developing hypertriglyceridemia with the use of PERIKABIVEN. In addition, patients with hypertriglyceridemia may have worsening of their hypertriglyceridemia with administration of PERIKABIVEN. Excessive dextrose administration may further increase such risk. Evaluate patients’ capacity to eliminate and metabolize the infused lipid emulsion by measuring serum triglycerides before the start of infusion (baseline value), with each increase in dosage, and regularly throughout treatment. If triglyceride levels are above 400 mg/dL in adults, stop the PERIPERIKABIVEN infusion and monitor serum triglyceride levels to avoid clinical consequences of hypertriglyceridemia such as pancreatitis.
To minimize the risk of new or worsening of hypertriglyceridemia, assess high-risk patients for their overall energy intake including other sources of lipid and dextrose, as well as concomitant drugs that may affect lipid and dextrose metabolism.
5.15 Interference with Laboratory Tests
Additions and/or revisions underlined:
The lipids contained in PERIKABIVEN may interfere with some laboratory blood tests (e.g., hemoglobin, triglycerides, bilirubin, LDH, and oxygen saturation) if blood is sampled before lipids in PERIKABIVEN have cleared from the bloodstream. Lipids are normally cleared after a period of 5 to 6 hours once the infusion is stopped. Therefore, conduct these blood tests at least 6 hours after the infusion is stopped.
6 Adverse Reactions
Addition of the following to the bulleted line listing:
- Vein Damage and Thrombophlebitis [see Warnings and Precautions (5.11)].
6.1 Clinical Trials Experience
Additions and/or revisions underlined:
…
In a randomized active-controlled, double-blind, parallel-group, multi-center study that included 152 neonates and 9 patients ranging in age from 29 to 153 days who were expected to require PN for at least 28 days, parenteral nutrition-associated cholestasis (PNAC), a precursor to PNALD, developed more frequently in Intralipid-treated patients than in patients treated with a 4-oil mixed lipid emulsion. Intralipid is the lipid emulsion component of PERIKABIVEN.
PNAC (defined as direct bilirubin >2mg/dl with a second confirmed elevation >2mg/dl at least 7 days later) occurred in 11.5% (9/78) of Intralipid-treated patients and 2.4% (2/83) of patients treated with a 4-oil mixed lipid emulsion. Most PNAC events occurred in patients who were treated for longer than 28 days.
The estimated cumulative incidence of PNAC is shown in the Kaplan-Meier cumulative incidence curve in Figure 1.
Figure 1: Cumulative Incidence Curve of Time to Parenteral Nutrition-Associated Cholestasis (PNAC) with Standard Error Bars
Monitor liver tests in patients treated with PERIKABIVEN and consider discontinuation or dosage reduction if abnormalities occur.
7 Drug Interactions
7.1 Ceftriaxone
Newly added subsection:
Precipitation of ceftriaxone-calcium can occur when ceftriaxone is mixed with calcium-containing parenteral nutrition solutions, such as PERIKABIVEN, in the same intravenous administration line. Do not administer ceftriaxone simultaneously with PERIKABIVEN via a Y-site. However, ceftriaxone and PERIKABIVEN may be administered sequentially if the infusion lines are thoroughly flushed between infusions with a compatible fluid [see Dosage and Administration (2.1)].
Deaths have occurred in neonates (28 days of age or younger) who received concomitant intravenous calcium-containing solutions with ceftriaxone resulting from calcium-ceftriaxone precipitates in the lungs and kidneys, even when separate infusion lines were used [see Contraindications (4), Use in Specific Populations (8.4)].
8 Use in Specific Populations
8.4 Pediatric Use
Additions and/or revisions underlined:
The safety and effectiveness of PERIKABIVEN has not been established in pediatric patients of any age.
Deaths in preterm infants after infusion of intravenous lipid emulsion have been reported [see Warnings and Precautions (5.1)]. Patients, particularly preterm infants, are at risk for aluminum toxicity [see Warnings and Precautions (5.14)].
Deaths have occurred in neonates (28 days of age or younger) who received concomitant intravenous calcium-containing solutions with ceftriaxone resulting from calcium-ceftriaxone precipitates in the lungs and kidneys, even when separate infusion lines were used. [see Contraindications (4), Warnings and Precautions (5.5)].
…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Extensive revisions; please refer to label